Malignant Hyperthermia
Conditions
Keywords
malignant, genetics, RYR1, CAC-NA1S, hyperthermia
Brief summary
The purpose of this study is to to determine the penetrance of known and probable pathogenic variants in genes and the factors that contribute to penetrance in a population of children and adults in the United States exposed to Malignant Hyperthermia (MH) trigger agents.
Detailed description
The purpose of the study is to determine how genetic mutations and variants in combination with non-genetic factors influence risk for MH in children who had general anesthesia with triggering agents and develop reliable predictive MH risk algorithms. Rationale: Once the factors responsible for MH risk are determined, it will be possible to better predict risk and develop better individualization of anesthetics such as tailored selection of intravenous anesthetics, regional anesthesia and avoidance of all triggering agents. The long-term goal is to tailor and improve safety of anesthetic and clinical care and to reduce mortality, morbidity and cost of care due to MH with right anesthetics and muscle relaxants for endotracheal intubations for an individual child.
Interventions
GENETICWhole exome sequencing
DNA sequencing of protein coding sections of all genes
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* Any English speaking person registered at NAHMR who has had a positive clinical manifestation of Malignant Hyperthermia * Any person with a positive Caffeine Halothane Contracture probTest (CHCT) or a close relative of a person that had these.
Exclusion criteria
* Any person who has NOT had a positive clinical manifestation of Malignant Hyperthermia * Any person with a positive Caffeine Halothane Contracture Test (CHCT) or NOT a close relative of a person that had these. Non-English speaking registrants will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Genetic comparison of MH phenotype subjects to that of the CHCT negative control subjects. | Within data collection period (5 years total). | MHS subjects and CHCT negative controls recruited from the North American MH Registry will have whole genome sequencing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Genomic factors that influence Malignant Hyperthermia. | Within data collection period (5 years total). | A Batesian inference algorithm based on multiple genetic risk factors assessed from DNA data collected |
| Induced pluripotent stem cells will be used for functional testing and gene editing | Indefinite - dependent on funding | Induced pluripotent stem cells will be made for future in-vitro analysis |
Countries
United States
Outcome results
None listed